For the preparation of biologically active organic compounds labelled with hydrogen isotopes it is known to use liquid-phase catalytical reactions of hydrogenation of unsaturated starting compounds or of dehalogenation of halide derivatives of the starting compounds. This results in the preparation of hydrogen isotope-labelled compounds containing only 1-2 hydrogen isotopes.
The progress in molecular biology and genetics is defined to a great extent by the availability of biologically active organic compounds labelled with hydrogen isotopes, since these compounds are indispensible for, e.g. carrying out research at the level of cell receptors or in the radioimmune diagnosis.
In this respect especially important are versatile methods for the preparation of isotope-labelled compounds pertaining to different classes of biologically active organic compounds.
Known in the art is a method for producing an isotope-labelled biologically active organic compound, namely a biogenic amine which comprises preparation of a mixture of solution of a biogenic amine in water with an inorganic vehicle and a catalyst, followed by treatment of the resulting mixture at a temperature of 280-303 K. with a gaseous hydrogen isotope, in particular with tritium, and a subsequent recovery of the desired product from the reaction mixture. (Radiochemical Radioanalytical Letters, vol. 46, No. 5, 1981, K.Verse et al., "Tritiation of organic compounds by the CESG method", p.307-316).
However, the degree of incorporation of the isotope (in particular, the value of specific radioactivity proportional thereto) in the labelled compound obtained by this method is 30-500 TBq/mol which corresponds to less than 0.5 hydrogen isotope atom per molecule of the labelled compound. Therefore, prepared by this method are biogenic amines with a low degree of incorporation of the label of a hydrogen isotope (tritium) at a non-uniform distribution thereof within the labelled compound molecule.
Known in the art is a method for preparing a biologically active organic compound (such as a biogenic amine, aminoacids, components of nucleic acids and the like) labelled with hydrogen isotopes which comprises preparation of a mixture of a solution of the starting compound in water or in an organic solvent with an inorganic vehicle and a catalyst, treatment of the resulting mixture at a temperature of 288-303 K. with a gaseous hydrogen isotope such as tritium, followed by isolation of the desired product (Uspekhi Knimii, vol.50, iss. 2, 1981, Moscow, L. A. Neuman "Incorportion of tritium into biologically active compounds by exchange methods", pp. 210-213).
The labelled compound obtained by this method has a specific radioactivity of 30-500 TBq/mol. In this case the isotope label is included mainly at the most reactive hydrogen atoms of the prepared compound.
Therefore, this method also enables preparation of biologically active compounds with a low degree of inclusion of the label of a hydrogen isotope (tritium) at a non-uniform distribution thereof within the molecule of the labelled compound.
It is an object of the present invention to increase the degree of incorporation of a label of a hydrogen isotope in a labelled biologically active organic compound.
It is another object of the present invention to obtain a labelled biologically active organic compound with a uniform distribution of a hydrogen isotope label within the molecule of the labelled compound.